TRANSGENIC EXPRESSION OF LYMPHOTOXIN RESTORES LYMPH-NODES TO LYMPHOTOXIN-ALPHA-DEFICIENT MICE

Lymphotoxin-alpha (LT alpha) has recently been demonstrated to be impo rtant in the development of lymph nodes (LN), Peyer's patches, and spl enic organization, including the development of germinal centers, To e lucidate the role of LT alpha in lymphoid organogenesis and the plasti city of the process, we examined LT alpha(-/-) mice in which an LT alp ha transgene under the control of the rat insulin promoter (RIPLT) is expressed in the pancreas, kidney, and skin. The LT alpha transgene re stored LN in LT alpha(-/-) mice, The reconstituted LN of RIPLT.LT alph a(-/-) mice had germinal center-like peanut agglutinin-positive region s, but lacked follicular dendritic cells. Although the LT alpha transg ene did not restore Peyer's patches or splenic architecture, it restor ed the ability of the spleen to form germinal centers and follicular d endritic cell networks. Lymphocytes isolated from the reconstituted LN showed normal proliferative responses to T and B tell mitogens and we re defective in their proliferative response to T-dependent Ag, and a decreased number of interdigitating, dendritic cells was apparent in t he RIPLT.LT alpha(-/-) mice LN. Expression of the RIPLT transgene in m ice deficient in LT beta did not reconstitute LN, suggesting an import ant role for LT beta in the mechanisms that reconstitute LN in RIPLT.L T alpha(-/-) mice, These data are the first to demonstrate reconstitut ion of LN in LT alpha(-/-) mice and show that the process of LN restor ation is amenable to manipulation with ectopic lymphotoxin.